Mecanismos dopaminérgicos e glutamatérgicos envolvidos no efeito modulatório da novidade sobre a persistência da memória de reconhecimento reconsolidada

Abstract

Memories can undergo reconsolidation after exposure to retrieval events that reactivate the memory. This event temporarily destabilizes the consolidated information, which is susceptible to interference and results in modifying the original memory. Exposure to novelty facilitates the formation and persistence of memory, involving synthesis and subsequent capture of proteins related to plasticity. Therefore, initially, we propose to investigate the effect of reactivation and exposure to novelty on the reconsolidation and persistence of object recognition memory (OR). Subsequently, we investigated the involvement of D1/D5 receptors, the PKA signaling pathway, and glutamatergic receptors in modulating the persistence of OR memory promoted by novelty, which are important systems for the modulation of memory by novelty. The sample consisted of 350 adult male Wistar rats; after being acclimated, all animals were subjected to the OR task (training session, reactivation, and reconsolidation or persistence memory tests). In the second study of this dissertation, all animals, before the OR task, underwent stereotaxic surgery under anesthesia to implant guide cannulas in the CA1 region of the hippocampus for subsequent drug infusion to pharmacologically manipulate the dopaminergic system, PKA via, and glutamatergic system. After reactivation in the OR, some animals were exposed to a new environment (novelty). At this time, some animals received an infusion of drugs to study the role of the dopaminergic and glutamatergic systems. To analyze the results, the object exploration time was converted into % of the total exploration time, and a one-sample t-test (or Wilcoxon test) was used for comparison with a theoretical average (50%). One-way ANOVA or Kruskal-Wallis test was used to compare the discrimination index between groups and for behavioral control tests. The significance level was P ≤ 0.05. In this dissertation, we demonstrate that exposure to novelty after the reactivation of learning improves memory reconsolidation, promoting its persistence through mechanisms dependent on the activation of PKA and AMPA. Furthermore, it appears that the effect of novelty on the persistence of reconsolidated OR memory does not depend on the activation of the dopaminergic system in the hippocampus.